Related Experiment Video

Updated: Jun 12, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

The c-Abl tyrosine kinase stabilizes Pitx1 in the apoptotic response to DNA damage

Tomoko Yamaguchi1, Yoshio Miki, Kiyotsugu Yoshida

  • 1Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Japan.

Apoptosis : an International Journal on Programmed Cell Death
|June 22, 2010
PubMed

Insights

Nuclear c-Abl tyrosine kinase increases human pituitary homeobox 1 (Pitx1) expression post-transcriptionally, promoting apoptosis after DNA damage. This pathway is independent of p53 and can be inhibited by blocking c-Abl kinase activity.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Genetics

Background:

  • The c-Abl tyrosine kinase accumulates in the nucleus during the DNA damage response and induces apoptosis.
  • The precise mechanisms by which nuclear c-Abl triggers apoptosis remain largely unelucidated.

Purpose of the Study:

  • To investigate the role of nuclear c-Abl in apoptosis induction following DNA damage.
  • To identify downstream targets and mechanisms modulated by c-Abl in response to genotoxic stress.

Main Methods:

  • Assessing human pituitary homeobox 1 (Pitx1) expression levels after DNA damage.
  • Analyzing the effect of c-Abl overexpression and inhibition on Pitx1 phosphorylation and apoptosis.
  • Evaluating the p53-independence of Pitx1-mediated apoptosis.

Main Results:

  • DNA damage increases Pitx1 transcription factor expression.
  • c-Abl modulates Pitx1 expression at the post-transcriptional level, inducing its tyrosine phosphorylation.
  • Overexpression of Pitx1 significantly induces apoptosis, irrespective of p53 status.
  • Inhibition of c-Abl kinase activity reduces Pitx1-mediated apoptosis.

Conclusions:

  • c-Abl plays a critical role in regulating Pitx1 expression during the apoptotic response to DNA damage.
  • The c-Abl/Pitx1 axis represents a novel pathway contributing to DNA damage-induced apoptosis, independent of p53.
  • These findings offer insights into the molecular mechanisms governing cell fate decisions following genotoxic insult.

More Related Videos

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence10:09

Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence

Published on: January 7, 2019

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells09:15

Tyramide Signal Amplification for the Immunofluorescent Staining of ZBP1-Dependent Phosphorylation of RIPK3 and MLKL After HSV-1 Infection in Human Cells

Published on: October 20, 2022

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...